The overall aim of this component is to provide an analytic framework for the assessment of empirical evidence on the burden of disease and injury attributable to major population exposures in the context of global Burden of Disease 2000 Study. It will do so by reviewing the conceptual issues in the calculation and interpretation of attributable fractions thereby providing a coherent conceptual framework for comparing disease and injury burden due to risk factor exposures. Related goals are to advance existing knowledge about risk factors for non-communicable disease, especially to advance knowledge about major blood-based risk factors through a large prospective study in a middle-income developing country (Mexico). The specific aims are: 1. Conceptual framework for comparative risk assessment: To provide a clear and coherent framework for comparing and interpreting the disease and injury burden attributable to specific population exposures. 2. Evidence of known risk factors: To provide reliable evidence on the importance and interactions of known risk factors for chronic diseases in a large, middle-income adult population. 3. Identification of new risk factors: To investigate and quantify the importance of other, blood-related factors as causes of premature death including genetic polymorphism, antibodies to many infective agents, hormones and other signal molecules, carious coagulation and inflammatory factors, micronutrients, and protein glycosylation. The empirical work will be based on a survey of 200,000 Mexican adults aged 40 years and older living in Coyoacan district, and repeated active morality follow-ups. Nested case-control studies will serve as the main methodology. These aims would be achieved chiefly by addition into already existing large prospective studies the collection and long-term storage of blood samples, which would be retrospectively analyzed for certain lipids, antioxidants, other biochemistries, antibodies and genetic polymorphisms in leucocyte DNA in "cases" who develop the particular disease of interest over the next few years, and individually matched "controls" who were then still alive and free of this disease.